糖基化
分泌物
生物
视网膜色素上皮
血栓反应素
细胞生物学
基质细胞蛋白
视网膜
生物化学
金属蛋白酶
细胞外基质
酶
作者
Susette Lauwen,Melissa Baerenfaenger,Sanne Ruigrok,Eiko K. de Jong,Hans J. C. T. Wessels,Anneke I. den Hollander,Dirk J. Lefeber
标识
DOI:10.1016/j.exer.2021.108798
摘要
Age-related macular degeneration (AMD) has been associated with protective genetic variants in the β1-3 glucosyltransferase (B3GLCT) locus through genome-wide association studies. B3GLCT mediates modification of proteins with thrombospondin type I repeats (TSR) that contain O-linked glucose β1-3 fucose and C-linked mannose glycosylation motifs. B3GLCT-mediated modification is required for proper secretion of TSR-containing proteins. We aimed to start understanding the role of B3GLCT in AMD by evaluating its effect on glycosylation and secretion of proteins from retinal pigment epithelium (RPE) cells. We generated B3GLCT knockout (KO) RPE cells and analyzed glycosylation and secretion of thrombospondin 1 (TSP1), a protein involved in cellular processes highly relevant to AMD. Glycopeptide analysis confirmed the presence of the glucose-β1,3-fucose product of B3GLCT on TSP1 in wildtype (WT) cells and its absence in KO cells. C-mannosylation was variably present on WT TSP1 and increased on TSR domains 1 and 3 in KO cells. Secretion of TSP1 was not affected by the absence of B3GLCT, even not when TSP1 was upregulated by TNFα treatment or when TSP1 was overexpressed in HEK293T cells. Future research is needed to elucidate the effect of the observed glycosylation defects in the context of AMD, which might involve functional loss of TSP1 or effects on other TSR proteins.
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